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Published on

04 Jan 2007

Abstract

Modeling metabolism has been generally based on the numerous
cellular reactions to be in steady state with respect to the
external fluxes on the cell boundary. The essence of this
“steady state” approach is the identification of all the
reaction rates (fluxes), both external and internal to the cell,
that together constitute metabolism. The steady state is
expressed by homogeneous algebraic equations that must be solved
to obtain the reaction rates. There are many more reactions than
species in metabolic systems resulting in a gross imbalance
between the number of unknowns and the number of equations.

Flux balance approaches have dealt with this
circumstance by seeking to identify fluxes that are
experimentally accessible, a strategy that continues to grow in
scope (such as by the systematic use of isotopic tracers), as a
means to enable estimation of other fluxes that are not
accessible. Resolution of the indeterminacy, however, has
depended on fortification with additional conceptual tools such
as maximizing the biomass yield. Regulatory processes, which are
a vital component of metabolism in that they determine what
reactions are in fact active in metabolism, are not an explicit
aspect of flux balance approaches.

A rational framework for modeling metabolism must
accommodate the prediction of all fluxes and in particular the
external fluxes which must reflect the consequences of metabolic
regulation. Such a framework is therefore forced to address
regulatory processes in a comprehensive way. In this regard, the
cybernetic modeling concept1 developed by our research group,
that has been evolving since the early eighties, has
progressively accommodated features of regulation that have not
been within the scope of other modeling approaches. This seminar
will focus on an exposition of this framework and its successes
together with an assessment of its promise in large scale
metabolic modeling and metabolic engineering.

Bio

Professor Ramkrishna has a Ph.D. in Chemical Engineering from
University of Minnesota in 1965. Currently he is the Harry
Creighton Peffer Distinguished Professor of Chemical
Engineering. Professor Ramkrishna's research group is motivated
by ideas in the application of mathematics to solving problems in
chemical and biochemical reaction engineering. Their research
ideas arise from linear (operator methods) and nonlinear analysis
of ordinary and partial differential equations, stochastic
processes, and population balance modeling involving integro-partial differential equations. Current research is on the
development of a dynamic framework for metabolic engineering
using cybernetic models with a view towards applications to the
production of bio-fuels such as ethanol from biomass, development
of population balance models for the evolution of crystal forms
in crystallizers, and in modeling cancer therapy with specific
focus on Acute Lymphoblastic Leukemia. He also has over 200
research paper publications and two books.

Credits

Funding support
by the NSF GOALI program (BES-0000961) and the
NSF Graduate Research Fellowship Program.

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